The major focus of our research is to understand the genetic and molecular basis of pattern formation in the nervous system. The nervous system of multicellular organisms is a complex network of diverse cell types with unique positions and patterns of connectivity. Understanding how these intricate patterns develop is a central problem in cell and developmental biology. During the development of the nervous systems of both invertebrates and vertebrates environmental cues and cellular interactions play important roles in the determination of cellular phenotypes and in pattern formulation. The compound eye of Drosophila is well suited for studying the cellular and molecular basis of pattern formation. Our research has been focused on the molecular genetic analysis of three genes: 1. genetic screens for mutations affecting pattern formation in the developing eye have led us to the discovery of a new gene, rap (retiiza aberrant in pattern). Our analysis demonstrates that rap gene function is critical for normal eye pattern formation. Several lines of evidence suggest that rap acts early to regulate the initial steps in ommatidial formation and is required only in the cell R8 for normal pattern formation, consistent with the notion that rap acts at the beginning of pattern formation. Our recent studies have shown that in rap mutants the R8 cell is abnormal and as a consequence rap mutant eyes lack the R7 cell. In addition in rap mutant cells R1 and R6 also fail to differentiate. These results are consistent with the inductive role played by the R8 cell and these results provide the first evidence of a role for R8 cell in the differentiation of R1 & R6. 2) Using a P element as a tag we have cloned 40 kb of the genomic DNA from the rap locus and a cDNA clone that maps within the locus has been isolated. We are presently carrying out germ line transfer experiments to define the physical limits of the rap gene and unequivocally ascertain the identity of the rap cDNA. These experiments are aimed at a genetic and molecular analysis of the rap gene with a view to understand the molecular nature of the rap gene product, its expression pattern and identify other gene products that interact with the rap gene. A significant portion of our research efforts are also directed towards understanding the molecular and genetic basis of the prune-Killer of prune interaction and its role in GTP homeostasis during development. We have recently shown that the pruize locus encodes a protein with similarities to the mammalian GTPase activating proteins (GAP). We have generated antibodies to prune fusion proteins expressed in bacteria and these antibodies are being used to purify the endogenous prune (Pn) protein from fly tissues. We are currently carrying out biochemical experiments to directly test for GAP like activity of the Pn protein. In addition we are using combined molecular and genetic screens to isolate extragenic suppressors of the pn-Kpn interaction. 3) Our laboratory is also interested in the molecular genetic basis of the function of rugose, a gene involved in neural pattern formation. A detailed genetic analysis of the locus has been carried out as a prerequisite to the molecular analysis.